JP2013503727A - Method and apparatus for evaluating a value representing the mass or concentration of a substance present in a patient's body - Google Patents

Abstract

The present invention relates to a method for evaluating a value representative of the mass or concentration of a substance consisting of a patient's tissue or body fluid, which relates to: Determining a relationship between the calculated or measured values; and b) determining whether the relationship meets a criterion. The present invention further relates to controllers, apparatus, and devices for practicing the present invention, and further to digital storage means, computer program products, and computer programs.
[Selection] Figure 1

Description

Technical Field and Summary of Invention

  The present invention relates to a method for evaluating a value representing the mass or concentration of a substance consisting of a patient's tissue or bodily fluid, the method reflecting a) the mass or concentration and the patient's distribution space or an approximation thereof. Determining a relationship between one or more calculated or measured value (s) and b) determining whether the relationship meets a criterion. The present invention further relates to controllers, apparatus and devices for carrying out the present invention, and further relates to digital storage means, computer program products and computer programs.

  In some situations, the mass or concentration of a substance present in the patient's body, eg, for diagnostic purposes only, or the patient's condition is actively controlled by modifying the substance's concentration or mass Therefore, it is necessary to check or monitor by the doctor in charge. Hemoglobin (Hb) is particularly such a substance.

  In practice, the concentration of hemoglobin (Hb, also known as Hgb, a metalloprotein that contains iron in red blood cells and carries oxygen) is measured by a blood sample to determine the patient's anemia status. A value that does not meet a given threshold is usually considered to be a sign of anemia that is defined as a decrease in the normal number of red blood cells (RBC) or as less than the normal amount of hemoglobin in the blood. It is.

  According to the present invention, a method for evaluating a value reflecting the mass or concentration or volume of a substance is proposed. Furthermore, a controller for carrying out the method according to the invention is provided, as well as an apparatus, a device comprising a controller, a digital storage means, a computer program product and a computer.

  The method according to the invention is defined by the combination of features of claim 1. Accordingly, in one aspect of the present invention, a method for evaluating or evaluating a value representing a mass, concentration, or volume of a substance composed of a patient's tissue or body fluid, or a change thereof, respectively, is a tissue or body fluid. One or more calculated or measured value (s) that reflect the mass or concentration or volume of the substance consisting of and, on the other hand, the patient's distribution space (or changes thereof), or an approximation thereof Determining a relationship between one or more calculated or measured value (s) that reflect and evaluating whether the relationship meets at least one criterion .

  The patient can be a human or an animal. Patients can be healthy or ill. The patient may or may not need medical care.

  The controller according to the invention is defined by the combination of features of claim 17. Thus, in another aspect of the invention, the controller is configured to carry out the method according to the invention.

  The device according to the invention is defined by the combination of the features of claim 18. Thus, in another aspect of the invention, the apparatus comprises a means for obtaining a value representing the volume, mass or concentration of a substance and / or a means for obtaining a value representing the distribution space or a change thereof, respectively. And at least one controller according to the invention.

  The device according to the invention is defined by the combination of the features of claim 22 for treating the blood of a patient. Thus, in another aspect of the invention, the device comprises at least one controller according to the invention or at least one apparatus according to the invention.

  The digital storage means according to the invention is defined by the combination of features of claim 25. Thus, in another aspect of the invention, the digital storage means, in particular a disc, CD, or DVD, is electrically capable of interacting with a programmable computer system so that the method according to the invention is carried out. Has a readable control signal.

  A computer program product according to the invention is defined by the combination of features of claim 26. Accordingly, in another aspect of the invention, a computer program product comprises program code stored on a machine-readable data medium for performing the method according to the invention when executed on a computer.

  A computer program according to the present invention is defined by the combination of features of claim 27. Thus, in another aspect of the invention, the computer program comprises program code for executing the method according to the invention when executed on a computer.

  It should be noted that whenever reference is made herein to the mass, or concentration, or volume of a substance, changes are also contemplated, whether explicitly stated or not.

  Embodiments can include one or more of the following features.

  In some embodiments, the calculated or measured state that reflects both the mass or concentration of the substance and the patient's distribution space is a pair of values of type “(x; y)”. Yes, x represents mass or concentration or change thereof, and y represents distribution space. Preferably, x and y are both measured simultaneously (eg, at the same minute, same time, same day, same week, same month, same hospitalization, outpatient, etc.) or by calculation based on such measurement results. It is obtained.

  In certain embodiments, the method includes using a value that reflects a mass or concentration obtained from at least one urine sample.

  In some embodiments, the method includes using a value that reflects a mass or concentration obtained from at least one blood sample.

  In some embodiments, the blood sample is taken from an extracorporeal blood circuit, and in other embodiments from a patient's blood vessel.

  In some embodiments, the method includes using a value that reflects a mass or concentration obtained from at least one tissue sample or at least one saliva sample.

  In certain embodiments, the values are also obtained from whole body measurements or from partial body measurements, such as measuring body content directly (and not by indirect methods such as urinalysis). It can be.

  In some embodiments, the whole body measurement is directed to the measurement of radioactive material (eg, potassium, etc.) with a whole body instrument known in the prior art. For such whole body measurements, the patient is isolated from the background radioactivity by suitable means, such as a chamber that shields the patient placed in the chamber from external radioactivity. By knowing the radioactivity of the radioactive substance to be measured and knowing the constant or constant ratio between the radioactive substance and the non-radioactive substance contained in the patient's body, the systemic content of the substance in question is determined. It becomes possible to ask.

  In some embodiments, determining whether a relationship meets at least one criterion means that the relationship is determined in advance or determined during the execution of the method according to the invention. Means to determine whether a request or request ("demand" and "request" are alternatives, examples, or synonyms for "criteria" in the context of the present invention) is satisfied. To do.

  For example, if the relationship is indicated by a number, the criterion can be one or more thresholds, and therefore the relationship is when the number representing the relationship is higher (or lower) than the threshold, or two or more If it is between the thresholds, the criteria will be met. Similarly, if the relationship is shown with a graphical symbol, or with a range, or as a curve, the criteria can be expressed in a graphical range, and therefore, to meet that criteria, the relationship is It should be above or below a predetermined graphical range. These examples are, of course, not to be understood as limiting the invention to these embodiments.

  In some embodiments, the relationship can be a ratio of values. For example, the relationship can be expressed by dividing “concentration (or mass, or change in concentration, or change in mass)” by “distribution space (or approximation of distribution space)”. In one embodiment, the relationship is expressed by “dividing the concentration of Hb by the relative excess of water”, which is related to the distribution space.

  In some embodiments, the distribution space is a body fluid. In some embodiments, the distribution space is body tissue, or body weight, or total body mass. In other embodiments, the distribution space is not body weight or total body mass. In some embodiments, the distribution space is a combination of body fluid and body tissue. In some embodiments, the distribution space is a space containing the material of interest. In some embodiments, the distribution space is a space where a major portion of the material in question is found in the patient's body. In some embodiments, the distribution space is limited to the space in the patient's body where the material in question is found.

  In certain embodiments, the distribution space is defined as blood volume (BV). Distribution space also includes ECW (extracellular water content), extracellular volume or fluid or mass of the body, ICW (intracellular water content), intracellular volume or fluid or mass of the body, plasma volume, TBW (total body water content). ), Body fluid, edema volume, lymph fluid, urine, total cell mass, or any other body fluid or volume thereof, and further combinations thereof. Furthermore, the distribution space included within the meaning of the present invention can be any ratio of the volumes mentioned previously, for example ECW / ICW.

  In some embodiments, the distribution space is defined as muscle mass, or volume. Distribution space can also be defined as fat mass or volume, bone mass or volume, and the like.

  In certain embodiments, the mass or concentration of the substance is an indicator of the patient's anemia status.

  In some embodiments, the indicator of anemia status is the total mass or concentration of hemoglobin (Hb), such as its change over time.

  In certain embodiments, the concentration or mass is measured directly from a blood sample, for example, or alternatively, by optical methods, for example, without drawing blood from a blood vessel, as is known in the art. The Additionally or alternatively, the value in question can be derived from a correct calculation of the substance, such as hemoglobin (Hb) or hemoglobin (Hb) status, or at least other values, parameters, etc. that allow a sufficient approximation. It is.

  In some embodiments, the indicator of anemia status is a hematocrit value (Hct), which is also understood as a concentration included in the present invention.

  In certain embodiments, a patient's anemia status is represented by only one value, such as Hb concentration, or Hct.

  In certain embodiments, the substance is at least any protein that is naturally produced in the patient's body, in particular hemoglobin, albumin, insulin, glucose, CRP, hormones, total protein, cells (eg, white blood cells), electrolyte, And non-endogenous substances, in particular, pharmaceutically effective substances such as cytostatics, non-physiological markers such as deuterium, and the like.

  In some embodiments, the distribution space is approximated based on a measurement of the patient's hydration state.

  In some embodiments, the distribution space reflects a patient's over-hydration (OH), relative over-hydration (relOH: over-hydration (OH) divided by extracellular water (ECW)), etc. And / or approximated, calculated or defined based on calculations. The definition of excess water (OH) is described in WO 2006 / 002685A1, where OH is equal to a * ECW + b * ICW + c * weight. The disclosures of WO 2006/002685 A1 are hereby incorporated by reference. It should be understood that OH can be determined by various methods, all of which are known to those skilled in the art. One of these methods involves measuring the dilution and calculating OH based on it.

  What has been described with reference to hemoglobin (Hb) in terms of concentrations, changes over time, values, calculations, approximations, etc., includes hematocrit value (Hct), blood volume (BV), excess water (OH), and relative This means that the same applies to excessive moisture (relOH).

  In some embodiments, the patient distribution space can be represented by age-corrected overhydration or relative overhydration (relAEOH). By doing so, for example, it is possible to obtain a more appropriate value by excluding some effects due to age.

  In some embodiments, the patient distribution space can be determined or defined as excess water (OH) divided by extracellular water content (ECW), or graphically displayed in such a manner. You can also

  In some embodiments, the patient distribution space is represented by only one value, in particular a value having a dimension of liters.

  In some embodiments, the distribution space is measured or approximated prior to dialysis or is based on the patient's pre-dialysis value.

  In some embodiments, the pre-dialysis (pre-Dx) value or calculation can be the acquired data just before starting the next dialysis treatment, ie, at the moment or minute. However, the present invention is not limited to this. Data can also be acquired at any other time. The pre-Dx data appears to be more stable than the other data. Therefore, there can be advantages to using that data.

  In some embodiments, the target range is defined by a diagram that represents both the mass, concentration, or volume of a substance, or a change thereof, and the patient's distribution space, or an approximation thereof. The target range may alternatively be a target area. The figure can alternatively be a plot. The figure can be an orthogonal coordinate system, also called a “rectangular coordinate system”. In the graphical representation of the figure, the mass, concentration, or volume of a substance, or change thereof, can be shown relative to the distribution space, and vice versa.

  In some embodiments, the criterion is a threshold value or a combination of threshold values.

  In certain embodiments, at least one criterion is preset or predetermined.

  In some embodiments, at least one criterion is variable.

  In certain embodiments, the method further includes determining a criterion.

  In some embodiments, the criteria are determined during the performance of the method according to the invention.

  In one embodiment, the regression lines are calculated based on measurements or results that reflect the mass (or concentration, or volume, respectively, or change thereof) and the distribution space, respectively, and the regression lines for each other. And evaluate the position between the target range. With respect to each other, it can be understood as “above”, “below”, “side by side”, “inside”, “crossing”, and the like. The relative position can be attributed to a certain degree or numerical value.

  In some embodiments, the criteria may be based on classification, in particular, Bayesian classification. It is further contemplated to define criteria based on fuzzy logic. Classification can also be achieved by nearest neighbor methods, neural networks, and the like.

  In an embodiment, the regression line is calculated based on the measured value or the calculation result. The regression line can represent any appropriate function.

  In some embodiments, the value for mass or concentration and the value for distribution space are obtained in one opportunity. “One opportunity” can be understood as a specific time, such as a range of minutes or hours. It can also be a day or the duration of one treatment, in particular one dialysis treatment. “One opportunity” can also be understood as the time a patient spends in the clinic for treatment.

  In certain embodiments, the method includes classifying the evaluation results.

  In some embodiments, the method according to the present invention includes plotting or illustrating a regression line and / or target range, as appropriate.

  In some embodiments, the method includes displaying whether the criteria are met (whether) in a table, spreadsheet, chart, or the like.

  In some embodiments, whether the criteria are met is determined based on only two values: one value that reflects the mass or concentration of the substance and one value that reflects the distribution space. Is done.

  In one embodiment, the two values are represented by only one point in the appropriate graphic.

  In some embodiments, the determination can be made at that one point, or just these two values.

  In certain embodiments, one or all values considered to determine the relationship reflect the corresponding mass, volume, concentration in an absolute manner. That is, changes over time remain unconsidered. Thus, any value that reflects mass, concentration, or volume can be static.

  Further, in some embodiments, the value reflecting the mass, concentration, or volume of the substance is obtained by subtracting the value, eg, by subtracting the first concentration value from the second concentration value. There is nothing.

  In some embodiments, time constants, or time variables, or parameters are not considered or included to determine the relationship. In particular, mass, concentration, or volume values are not multiplied by time values.

  In some embodiments, the slope of the regression line is further considered in the determining step. The slope can be estimated or can be known (approximately) from previous measurements from the same patient, or a corresponding patient, or a collection of (healthy or sick) patients.

  In some embodiments, the y-offset of the regression line is also considered in the determining step. “Y” can relate to the mass, concentration, or volume of a substance when displayed in a diagram, for example, in a Cartesian coordinate system, or can relate to a hydration value such as, for example, relOH.

  In some embodiments, the value reflecting the distribution space is measured in liters (l).

  In some embodiments, mass or concentration (or changes thereof) and patient distribution space are calculated and / or measured. Measurements and calculations can be performed by any method known in the art using any suitable device. In particular, in some embodiments, each data can be obtained by measuring Hb from a blood sample and / or Hb from blood contained in an extracorporeal blood line with an appropriate monitor. The measurement can be performed by measuring the optical characteristics of blood with an optical sensor and / or evaluating acoustic characteristics such as the transition time and / or propagation velocity of the ultrasonic pulse with the ultrasonic sensor.

  Any suitable monitor can also be used to determine the hydration state, such as a monitor based on bioimpedance or dilution techniques.

  The monitor for acquiring data related to the hydration state can be the monitor described in WO 2006/002685 A1. The disclosures of WO 2006/002685 A1 are incorporated into this application by reference. Of course, it should not be understood that the present invention is limited to monitors that determine the hydration status of a patient by measuring the bioimpedance described in WO 2006/002685 A1. Other methods known in the art are also contemplated and encompassed by the present invention, such as dilution measurements, and any other methods known to those of skill in the art.

  In some embodiments, to improve the patient's anemia status, the dose of the drug administered to the patient is determined or adjusted based on the results of determining whether the criteria are met.

  In some embodiments, the distribution volume should be adjusted. This can be achieved by administration of substances such as diuretics and / or dialysis, for example ultrafiltration. In some embodiments, a pharmaceutically effective substance is administered. In one embodiment, the assessment results for the criteria are output in the form of advice on how to treat the patient.

  In some embodiments, the criteria are set, determined, or predetermined.

  In certain embodiments, the device is a monitor for obtaining information about the distribution space or an approximation thereof, eg, the hydration state. Examples of such monitors are described above. To avoid unnecessary repetition, a monitor generally refers to a hydration monitor that produces a result that reflects a hydration state based on a bioimpedance signal, a dilution method, or any other method known in the art. .

  In some embodiments, the apparatus further comprises an output device for outputting the results provided by the controller. The output device can be a monitor having a display, plotter, printer, or any other means for providing output.

  In one embodiment, the device is a “Replacement of Renal Function by Dialysis” by Drukker, Parson, and Maher, Kluwer Academic Publisher, Vol. Provide a monitor for measuring Hb concentration (eg, in g / dl) and / or determining blood volume by any monitor described on pages 397-401 (“Hemodialysis machines and monitors”) .

  In some embodiments, the monitor is configured to measure a blood volume and / or concentration of a substance, particularly Hb, by measuring conductivity.

  In certain embodiments, the monitor is configured to measure the blood volume and / or concentration of a substance, particularly Hb, by measuring optical density.

  In some embodiments, the monitor is configured to measure the blood volume and / or concentration of a substance, particularly Hb, by measuring the viscosity.

  In some embodiments, the monitor is configured to measure the blood volume and / or concentration of a substance, particularly Hb, by measuring the density.

  In some embodiments, the monitor is one or more corresponding probes and / or one or more for performing measurements, such as a conductivity sensor, light sensor, viscosity sensor, density sensor, and the like. A plurality of sensors are provided.

  In certain embodiments, the device can be used to treat a patient by dialysis.

  In other embodiments, the device can be used to treat a patient (or patient's blood) by hemofiltration, ultrafiltration, hemodialysis, and the like.

  Embodiments can provide one or more of the following advantages.

  According to the present invention, it is possible to easily determine the gain or loss of a parameter or value that is caused by or accompanied by a specific value that reflects the mass or concentration of the substance and that represents a specific condition (such as anemia condition) of the patient. However, the parameters can be exacerbated by the volume of the distribution space or the actual hydration state.

  For example, in current practice, non-physiological concentrations of a substance (eg, a very low hemoglobin level of less than 8 g / dl) in a patient (eg, having a heart or kidney disorder) by altering metabolism (eg, , By administering an erythropoiesis promoter), or by correcting its volume or space of distribution (eg, by ultrafiltration treatment, or by administering a diuretic), or a combination of both. It is not clear whether or not In other words, the measured Hb concentration is “artificially” altered or diluted to varying degrees depending on the degree of water overhydration (hyperhydration) or water deficiency (hyperhydration). It may seem that it can be done.

  In severe overhydration, the blood volume can be expanded beyond normal levels, so that even if the absolute red blood cell mass is appropriate in normal hydration situations, Hb The concentration will decrease. As an example, a 3 liter (l) excess of water will increase 1 liter (l) in the blood volume (BV), and therefore there are 2 liters in the interstitial space. Because the relative changes in BV and OH are the same due to this typical 2: 1 relationship, instead of blood volume (which can be measured more easily than blood volume) for evaluation based on criteria. It is possible to use a value representing excess water. Assuming a typical blood volume (BV) of 5 liters, this would represent a 20% increase. A 20% decrease in Hb concentration should be, for example, 11.5-9.2 g / dl. Such low Hb levels will increase erythropoietin (EPO) dosing. Thus, the patient may benefit more from correcting the patient's overhydration (OH) than from correcting the Hb by the drug.

  All or some of the advantages mentioned above can also be found when the present invention is applied to other materials other than Hb, which are only used as examples herein.

It is the figure which plotted the state which reflects both an anemia state and a hydration state of a patient with a Hb-hydration excess figure. FIG. 2 is a diagram corresponding to the plot of FIG. 1 showing other patient data. FIG. 2 is a diagram corresponding to the plot of FIG. 1 showing other patient data. It is a figure corresponding to the plot of FIG. 1 in a more general description. It is a figure corresponding to the plot of FIG. 1 which shows the data of another patient. It is a figure corresponding to the plot of FIG. 1 which shows the data of another patient. It is a figure corresponding to the plot of FIG. 1 which shows the data of another patient. FIG. 6 is a diagram corresponding to the plot of FIG. 1 showing the patient data of FIG. 5. It is a figure corresponding to the plot of FIG. 1 which shows the data of another patient. FIG. 2 is a diagram corresponding to the plot of FIG. 1 showing only one measurement data. 1 shows a first device comprising a controller for carrying out the method according to the invention. FIG. -Figure 2 shows a second device comprising a controller for carrying out the method according to the invention;

  Other aspects, features, and advantages will be apparent from the description, drawings, and claims. The following example relates to Hb as the substance in question, and the distribution space is approximated by the measured relative water overload of the patient. However, it should not be understood that the present invention is limited to this example.

  FIG. 1 shows 19 measurement results that reflect both anemia and hydration status of the patient plotted in the figure. The figure is an orthogonal coordinate system showing Hb for relAEOH (relative water overload, corrected for age). Nineteen measurement results obtained from the patient in question (here, anonymized as “subject 15”) are indicated by a small circle 1.

  A regression analysis was performed based on the 19 measurement results. The obtained result is added as a regression line 3 to FIG.

  In FIG. 1, the target range 5 is further shown. The shape and position of the target range 5 are, for example, selected or determined based on personal experience and data. However, the present invention should not be understood as being limited thereto. Both the shape and position of the target range 5 can be determined in different shapes if necessary. In particular, the target range can reflect findings from previous measurements of the same patient. Furthermore, the target range can reflect knowledge based on patient measurements that are comparable to the patient in question, eg, suffering from the same disease.

  The criterion to be satisfied in the example of FIG. 1 is whether the regression line 3 crosses the target range 5. As can be seen from FIG. 1, the regression line 3 clearly crosses the target range 5, so it is clear that the criterion is met in FIG. 1, see the portion 3 ′ of the regression line 3.

  In the example of FIG. 1, the anemia status is, for example, “Replacement of Renal Function by Dialysis” by Drukker, Parson, and Maher, Kluwer Academic Publisher, Vol. Reflected by the Hb concentration (in g / dl) obtained by any monitor described on pages 397-401 ("Hemodialysis machines and monitors"). Again, each disclosure on pages 397-401 is incorporated herein by reference. The initial value was obtained after dialysis treatment started. It should be noted that the monitors discussed herein can be used to monitor or detect blood volume (or changes thereof), which is considered as another distribution space within the meaning of the present invention. I want.

  Further, in the example of FIG. 1, the hydration state is expressed as relative excess water (excess water (OH) measured by the monitor as described above with reference to WO 2006 / 002685A1). Reflected by the amount of external moisture (ECW). These values were obtained before starting dialysis treatment ("pre-Dx").

  For any of the values mentioned herein, a time average value (in terms of Hb) can be used. In addition, analysis shows that the initial value during treatment has the best correlation to weight and OH changes. The reason may be due to the presence of many disturbances in the microcirculation and macrocirculation towards the end of treatment. Therefore, it may be possible to measure a more reliable value after 30 minutes without performing the ultrafiltration method (to confirm that refilling has stopped).

  Target range 5 can be understood as a possible pre-Dx target range for both Hb and relOH.

  As can be seen from FIG. 1, as the patient's hydration state decreases, the Hb concentration increases due to the (reverse) dilution effect, but the red blood cell mass remains constant and the total Hb mass (in concentration Is not constant).

  Since the regression line 3 showing a significant correlation between Hb and relOH moves through the target range 5, normalization of hydration by liquid management will automatically normalize Hb as well. . It appears that no further intervention is needed to manage the patient's anemia status, such as the administration of EPO, or its use.

  FIG. 2 shows a plot similar to that of FIG. 1 showing data for another patient (“Subject 22”). In FIG. 2, the regression line 3 ″ passes under the target range 5. The criteria applied here (ie the regression line 3 needs to cross or intersect the target range 5) are not met. Thus, the value representing the patient's anemia status may not return to normal after the hydration status has returned to normal. Thus, the patient increases the dose of such a substance by administering a substance that increases the patient's Hb concentration to return to normal or if the patient is already taking medication / taking the drug Therefore, there is a high possibility that a profit will be obtained.

  FIG. 3 shows a plot similar to that of FIG. 1 or 2 showing data for yet another patient (“subject 69”). In FIG. 3, the regression line 3 ″ ″ passes over the target range 5. Again, the criteria applied here are not met. Furthermore, the value representing the patient's anemia status may not return to normal after the (excess) hydration status has returned to normal. Thus, if a patient is administered substances that increase the patient's Hb concentration, such as EPO, the patient will almost certainly benefit from reducing the dose of these substances.

  As can be seen from FIG. 3, the evaluation result of the patient's anemia status according to the present invention is highly dependent on how the criteria are determined (in advance). For example, instead of determining the criterion that the regression line needs to cross the target range as in the example in the figure, only one, two, or more results are within the target range If it is defined that the condition is satisfied, the criterion is also satisfied in the case of the example shown in FIG.

  What has been described above with reference to FIGS. 1 to 3 is shown schematically in FIG. 4 for any patient receiving EPO. FIG. 4 shows a schematic concept of how the dose of EPO can be derived from the position (relative position) of the regression line in the plot. If a regression line 3 "" is found, it is advised to reduce the dose of EPO. The regression line calculated based on the measurements made after adapting (decreasing) the EPO dose should be the low line indicated by arrow 7 '. If a regression line 3 "is found, the patient appears to benefit from a high EPO dose. The regression line calculated based on the results of measurements made after adapting (increasing) the EPO dose should be a high line as indicated by the arrow 7 ''.

  It should be noted that only a few initial measurements are required to determine the regression line, ie, one result or point may already be sufficient. For example, results obtained from measurements made over a time period of 2-4 weeks should be sufficient.

  Although the shape of FIG. 5 is different from that of FIGS. 1-4, the “target corridor 5 ′” for a dose of a drug such as EPO, as shown in FIG. Can also be specified. The target passage 5 'is a more specific example of the target range 5 known from FIGS. It differs in that it is adapted to the individual regression line slope of the patient in question (here "subject 141"). When formed as shown in FIG. 5, the target passageway 5 'can help to allow early EPO adjustment even when normal hydration has not yet been achieved. . This can be particularly beneficial with respect to the long time constant between administration of EPO and red blood cell production (hematopoiesis). As can be seen from FIG. 5, the dose of EPO can already be increased at the start of the moisture reduction phase.

  As can be seen from FIG. 5, the criteria for assessing the patient's anemia status to be met by the present invention are also such that the regression line slope or slope is within the target range, particularly the rectangular range, or the main range. It can also be set as parallel or not. Further, the criteria may be whether the regression line is completely contained within the target range, whether the regression line crosses a certain predetermined portion of the target range, or a side of the target range, and so forth.

  FIGS. 6-9 show further examples of plots drawn from Hb and hydration measurements obtained from still other patients (“Subjects 73, 86, and 94”) and from the patient of FIG. ing. Pre-set criteria (ie, the regression line 3 needs to cross or intersect the target range 5) are not met by the patients of FIGS. 8 and 9, but the patients of FIGS. 6 and 7 It is satisfied.

  The figure shows that if the patient's reference line or regression line crosses the reference range, only the hydration state should be adjusted, and if the reference line or regression line passes above or below the metabolic process (eg Understand that it should be addressed (using EPO).

  FIG. 10 is a plot similar to that of FIG. 1 or 2 showing the concentration of Hb (g / dl) versus excess water (L or l), showing only one measurement data indicated by circle 1. Is shown. As can be seen from FIG. 10, the regression line 3 cannot be determined on the basis of only one measurement. From FIG. 10, in some situations, a regression line is needed to determine whether the criteria (here, whether the measurement represented by circle 1 is included in range 5) is met. It is further understood that there is no. In any case, the preset criteria are not satisfied in the example of FIG.

  As can be seen from any of the figures discussed above, whether the criteria are met by each patient's specific anemia and hydration status, how the criteria are set or determined in advance It depends on.

  FIG. 11 shows a device 9 comprising a controller 11 for carrying out the method according to the invention. The device 9 is connected to an external database 13 containing the measurement results and data necessary for the method according to the invention. The database 13 can also be an internal means. The device 9 can optionally have means 14 for inputting data to the controller 11 or to the device 9. Such data can be information regarding the mass, volume, and concentration of the substance, as described above. Such data input to the device 9 may also be information about the patient distribution space or an approximation thereof in addition or instead. Furthermore, the reference can be input by the input means 14. However, the criteria could alternatively be stored in the database 13 or any other storage. The criteria can be calculated or determined by the controller 11 or by any other product configured or interconnected by the device 9. Results such as evaluations, calculations, comparisons, determinations, etc. performed by the controller 11 and / or the device 9 can be displayed on the monitor 15 or can be plotted by a plotter optionally included, but not shown. 13 or any other storage means. The database 13 can further comprise a computer program that, when executed, starts the method according to the invention.

  In particular, the controller 11 may include one or more calculated or measured value (s) that reflect the mass or concentration or volume of a substance consisting of tissue or body fluid and the patient's distribution space or approximation thereof. And the relationship may be configured to meet at least one predetermined criterion.

  As can be seen from FIG. 12, for the corresponding measurement, the device 9 is connected (by wire or wirelessly) to the bioimpedance measuring means 17 as an example of means for measuring or calculating the hydration state or the excess water state. can do. In general, the means for measuring or calculating the hydration state or the excess water state is in addition to or instead of the external database 13 containing the measurement results and data necessary for the method according to the invention (ie. As an alternative).

  The bioelectrical impedance measuring means 17 can automatically compensate for the influence on impedance data such as contact resistance.

  An example for such a bioimpedance measurement means 17 is a device from Xitron Technologies sold under the trademark Hydra ™ further described in WO 92/19153, That disclosure is expressly incorporated into this application by reference.

  The bioimpedance measuring means 17 can include various electrodes. In FIG. 12, only two electrodes 17a and 17b attached to the bioimpedance measuring means 17 are shown. Of course, additional electrodes are also contemplated.

  Each suggested electrode can be equipped with two or more ("secondary") electrodes as well. The electrodes can include current injection (“secondary”) electrodes and voltage measurement (“secondary”) electrodes. That is, the electrodes 17a and 17b shown in FIG. 12 can include two injection electrodes and two voltage measurement electrodes (ie, a total of four electrodes).

  Generally speaking, the means for measuring or calculating the hydration state or the over-hydration state are based on weighing means for inputting the necessary data, keyboard, touch screen, etc. It may be provided by a connection or communication link, any other input means, etc.

  Similarly, the device 9 can be used to re-provide a substance that can be provided again in addition to or instead of (ie as an alternative to) the external database 13 already containing the measurement results and the data necessary for the method according to the invention. There may be means 19 for measuring or calculating means for obtaining a value reflecting mass, volume or concentration.

  The means 19 can be provided as a weighing means for inputting the necessary data, a keyboard, a touch screen, etc., and as a sensor, an interconnection or communication link with a laboratory, a Hb concentration probe, any other input means, etc. .

  Again, it should be noted that the figures relate to Hb / anemia and relOH / hydration using examples that show how one embodiment of the invention can be implemented. The figures should not be understood as limiting.

Claims (27)

A method for evaluating a value representing a mass, concentration, or volume of a substance comprising a patient's tissue or body fluid, comprising:
One or more calculated or measured value (s) reflecting the mass, the concentration, or the volume of the substance comprising the tissue or the body fluid, and the patient's distribution space or its Determining a relationship between one or more calculated or measured value (s) reflecting the approximation;
Determining whether the relationship satisfies at least one criterion;
Including methods.   The method of claim 1, wherein the at least one value that reflects the mass, the volume, or the concentration of the substance is obtained from a blood sample.   The method according to claim 1 or 2, wherein the at least one value reflecting the mass, the volume or the concentration of the substance is obtained from a urine sample.   4. The method according to any one of claims 1 to 3, wherein the at least one value reflecting the mass, the volume or the concentration of the substance is obtained from a tissue sample.   The substance comprises at least any protein naturally produced in the patient's body, in particular hemoglobin, albumin, insulin, glucose, CRP and a non-endogenous substance, in particular a pharmaceutically effective substance. 5. The method according to any one of claims 1 to 4, comprising a group.   The method according to claim 1, wherein the mass or the concentration of the substance or a change thereof is an indicator of the anemia state of the patient.   The method of claim 6, wherein the indicator of the anemia state of the patient is hemoglobin (Hb) concentration, total mass, or change over time.   The method according to claim 6 or 7, wherein the indicator of the anemia state of the patient is a hematocrit value (Hct) or a change thereof over time.   The method according to claim 1, wherein the distribution space of the patient is a measured or calculated value of blood volume (BV).   10. The distribution space of the patient according to any one of claims 1 to 9, wherein the distribution space of the patient is an approximation based on a measured or calculated value reflecting the relative excess water (relOH) of the patient. The method described.   11. The distribution space of claim 1-10, wherein the distribution space is measured or approximated before dialysis, or based on the patient's pre-dialysis value, or measured or approximated during or after dialysis treatment. The method according to any one of the above.   12. A method according to any one of the preceding claims, comprising defining in the figure a target range that reflects the mass or concentration of the substance and the distribution space or approximation thereof.   Calculating a regression line based on measured or calculated values that together reflect the mass or concentration of the substance comprising tissue or body fluid and the distribution space of the patient, or an approximation thereof, and 13. The method of claim 12, comprising determining a regression line and any overlap between the target ranges.   14. The method of any one of claims 1 to 13, comprising calculating and / or measuring a parameter reflecting the mass or the concentration of the substance and / or the distribution space of the patient or an approximation thereof. Method.   Determine the dose of the drug to be administered to the patient or to improve the patient's anemia status based on the acquired relationship between the calculated or measured value (s) and the criteria 15. A method according to any one of the preceding claims, comprising the step of adjusting.   16. A method according to any one of the preceding claims, comprising determining the criteria.   A controller configured to perform the method of any one of claims 1-16. A device for evaluating a value representing the mass or the concentration of a substance consisting of a patient's tissue or body fluid,
Means for acquiring the distribution space of the patient's body, or a value reflecting the approximation or change thereof, and / or acquiring the mass, volume or concentration of the substance, or a value reflecting the change thereof Means for
At least one controller according to claim 17;
A device comprising:   The means for obtaining a value reflecting the distribution space, or an approximation or change thereof, is a means for measuring or calculating the distribution space, or an approximation or change thereof, in particular measuring the hydration state or excess water. 19. An apparatus according to claim 18, comprising or means for calculating, or wherein said means for obtaining a value comprises such means for measuring or calculating.   The means for obtaining a value reflecting the mass, the volume or the concentration of the substance is a weighing means, a means for determining a patient's blood volume, a keyboard, a touch screen, and the substance, in particular blood; Said means for measuring or obtaining at least one of means for measuring or calculating said concentration, said volume, and / or said mass, or change thereof, of hemoglobin (Hb) therein 20. An apparatus according to claim 18 or 19, wherein consists of such means for measuring or calculating.   21. The apparatus according to any one of claims 18 to 20, further comprising an output device for outputting a result provided by the controller.   A device for treating a patient's blood comprising at least one controller according to claim 17 or at least one apparatus according to any of claims 18-21.   23. The device of claim 22, wherein the device treats a patient by dialysis.   24. The device of claim 23, wherein the device is treated by hemofiltration, ultrafiltration, and / or hemodialysis.   17. A disc, in particular a CD, with electrically readable control signals capable of interacting with a programmable computer system so that the method according to any one of the preceding claims is carried out. Or digital storage means which is a DVD.   A computer program product comprising program code stored on a machine-readable data medium for performing the method of any one of claims 1-16 when executed on a computer. A computer program having program code for executing the method according to any one of claims 1 to 16 when executed on a computer.

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